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While its immediate clinical impact is well established, the long\u2010term multisystem comorbidities of AP remain underexplored. Clarifying the temporal sequence of these comorbidities is essential for improving patient outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a phenome\u2010wide association study (PheWAS) to investigate the associations between AP and 1429 clinical outcomes using Cox proportional hazards models in the UK Biobank. A total of 4767 AP cases were matched 1:10 with controls through birth year, sex, and Townsend deprivation index using incidence density sampling. Disease trajectory analyses were performed to characterize sequential diagnostic patterns of AP\u2010associated comorbidities. Genetic approaches including polygenic risk score analysis, linkage disequilibrium score regression (LDSC), and two\u2010sample Mendelian randomization (TSMR) were used as a genetic triangulation framework to provide complementary evidence for the observational findings and explore shared genetic architecture and potential causal relevance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Over an average follow\u2010up of 13.7\u00a0years, AP was associated with 250 incident comorbidities and all\u2010cause death. Three major temporal patterns of AP\u2010related comorbidities were identified, beginning with digestive diseases (e.g.,\u00a0chronic pancreatitis), metabolic and endocrine disorders (e.g.,\u00a0diabetes mellitus), as well as other systemic conditions (e.g.,\u00a0depression). Subsequently, increased risk of organ dysfunction such as myocardial infarction, renal failure, respiratory failure, and then dystrophia, sepsis, septicemia, acidosis followed by all\u2010cause death were observed. The polygenic PheWAS, LDSC, and TSMR analyses provided complementary support for selected associations, including chronic pancreatitis, cyst and pseudocyst of pancreas, duodenal ulcer, diabetes mellitus, anxiety disorder, asthma, and myocardial infarction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study characterizes long\u2010term multisystem comorbidity patterns associated with AP, highlighting temporal diagnostic patterns linked to adverse outcomes. These findings support the need for multidisciplinary monitoring and targeted interventions to mitigate long\u2010term risks in AP patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ueg2.70283","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T07:06:56Z","timestamp":1789715216000},"source":"Crossref","is-referenced-by-count":0,"title":["Long\u2010Term Multisystem Comorbidity Patterns in Acute Pancreatitis: Insights From Observational and Genetic Analysis"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1402-9583","authenticated-orcid":false,"given":"Tianyi","family":"Che","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Ruijin Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Affiliated Hangzhou First People's Hospital School of Medicine Westlake University  Hangzhou Zhejiang China"},{"name":"Department of Gastroenterology The Third Xiangya Hospital of Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Interventional Center of Valvular Heart Disease Beijing Anzhen Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4937-9168","authenticated-orcid":false,"given":"Xixian","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Third Xiangya Hospital of Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital of Zhejiang 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University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Ruijin Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2029-8831","authenticated-orcid":false,"given":"Duowu","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Ruijin Hospital School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit J.","family":"Arsenault","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec\u2014Universit\u00e9 Laval  Laval Qu\u00e9bec Canada"},{"name":"Department of Medicine Faculty of Medicine Universit\u00e9 Laval  Laval 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